WHEN TWO ANTIBODIES COLLIDE: DUAL-POSITIVE RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS IN NEPAL AND ITS GLOBAL PARALLELS

Anti-neutrophil cytoplasmic antibody (ANCA) and anti-glomerular basement membrane (anti-GBM) antibodies are found together in double-positive patients (DPPs), a rare subgroup of patients with systemic vasculitis. DPPs have a distinct immunological and clinical profile, with myeloperoxidase (MPO)-ANCA antibodies predominating and sporadic triple positivity. Like their single-positive counterparts, DPPs exhibit multi-organ symptoms with renal involvement. Features of ANCA-associated vasculitis and anti-GBM illness are both visible in renal histology. DPPs frequently have reduced renal recovery despite severe immunosuppression, which makes conventional therapy options difficult to implement. A poor overall and renal prognosis is caused by DPP, which is linked to the traits of two distinct forms of vasculitis. There are various cases in the literature on DPPs and their epidemiological features, clinical presentation, and therapeutic outcomes.

We report here a case of DPPs in a Nepalese woman, summarize other studies in Nepal, and compare the epidemiological features, clinical presentation, and therapeutic outcomes with global data.

A 74-year-old female former smoker was referred to our hospital's emergency department with fever, cough, red urine, nausea, and generalized weakness, all of which were accompanied by rapidly deteriorating renal function. There were no comorbidities in the patient's medical history, and no other known connective tissue or autoimmune diseases. Her initial examination indicated anemia, elevated inflammatory parameters, renal function impairment, the presence of numerous red blood cells in her urine, and Grade 3 bilateral medico-renal disease. Further tests revealed a positive MPO/p-ANCA (titre = 73) and Anti-GBM (titre = 101). She was given intravenous methylprednisolone 500mg, oral cyclophosphamide 500mg, and prednisolone 50mg, as well as symptomatic therapy and multivitamin supplements. She is doing well right now and is scheduled for a biopsy.

After comparing cases with worldwide data (Table 1), we found that the mean age of Nepalese patients was lower, with a higher female prevalence and similar presenting symptoms of cough, fever, and shortness of breath. In every study, more than half of patients requiring Renal Replacement Therapy were treated with similar treatment regimens. Most patients had a kidney biopsy, which revealed crescent formation and IgG linear deposition. The majority of them had a poor prognosis, and some had deceased as a result of diffuse alveolar hemorrhage, pneumonia, or neurological complications.

Table 1: Comparison of Nepalese population with global studies

DPPs frequently have reduced renal recovery despite severe immunosuppression, which makes conventional therapy options difficult to implement. In between infections, patients are less likely to respond, which often leads to treatment interruptions.  DPP patients require frequent long-term monitoring and should be evaluated for maintenance immunosuppression. Thus, knowing the patient's ANCA and anti-GBM antibody status in patients with RPGN is critical for guiding management and predicting prognosis. Further research should focus on this condition's most effective treatment strategy, as it is a distinct entity.